Nanomolar L-DOPA facilitates release of dopamine via presynaptic .BETA.-adrenoceptors: Comparative studies on the actions in striatal slices from control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-treated C57 black mice, an animal model for pa
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概要
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Effects of L-DOPA (0.1-10, 000 nM) on spontaneous release (Sp), evoked release (S) and tissue content (C) of dopamine (DA) were studied comparatively in superfused striatal slices from control and 1-methyl-4-phenyl-1, 2, 3, 6-tetrahy-dropyridine (MPTP)-treated C57 black mice to obtain evidence for L-DOPA-induced facilitation of S via presynaptic β-adrenoceptors. In control slices, isoproterenol-induced concentration-dependent increases in S were propranolol-sensitive. L-DOPA at 0.1-3 nM tended to increase the S of DA with a concomitant tendency of increases in Sp. L-DOPA at 10-1 × 10<SUP>4</SUP> nM concentration-dependently increased Sp. L-DOPA at 1-10 μM tended to increase S and 10 μM increased C. In slices from MPTP-treated mice, the absolute amounts of Sp, S and C decreased by half compared to those in control slices. L-DOPA at 3 nM facilitated S without increasing Sp. This facilitation was antagonized by propranolol at 3 nM. L-DOPA at 30 nM decreased S from the peak facilitation, which contrasted with no effect in the control slices. However, 10-100 nM L-DOPA increased Sp more markedly than that in the control slices. L-DOPA at 100 nM increased S and C, which contrasted with no effect in the control slices. In conclusion, nanomolar L-DOPA facilitates the S of DA via presynaptic β-adrenoceptors at concentrations lower than those required to induce conversion to DA even in striatal slices from the MPTP-treated mice model for Parkinson's disease. In model slices, susceptibilities of the Sp, S and C of DA to exogenous L-DOPA could be determined by a balance between degeneration-induced reduction in DOPA-decarboxylase activities and "up-regulation" on the activities of surviving DA neurons.
- 公益社団法人 日本薬理学会の論文
著者
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Arai Nobutaka
Department For Neuroscience Tokyo Metropolitan Institute Of Neuroscience
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Misugi Kazuaki
Department Of Pathology Yokohama City University
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Goshima Yoshio
Department Of Molecular Neuropharmacology Yokohama City University Graduate School Of Medicine
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MISU Yoshimi
Department of Pharmacologv, faculty of Pharmaceutical Scieuces, Kyoto University
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Arai Nobutaka
Departments of Pathology, Yokohama City University School of Medicine
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Misu Yoshimi
Departments of Pharmacology, Yokohama City University School of Medicine
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